We have observed the development of interferon resistance in a number of patients receiving interferon alfa-2a treatments and have correlated it with the development of anti-interferon antibodies. Of 16 patients with neutralizing antibodies to interferon alfa-2a, 6 developed clinical resistance to this therapy. The reason why the remaining 10 patients remained sensitive to interferon in the face of antibodies is not clear, and it is the purpose of this trial to look at effects that these antibodies might have on the biological effects of interferon alfa-2a in patients with hairy cell leukemia. All patients entered on this study have hairy cell leukemia and will have been treated with interferon in the past. Patients will receive a single dose of interferon alfa-2a and serial assessments of 2'-5'oligoadenylate synthetase activity in peripheral blood mononuclear cells, serum neopterin levels, interferon pharmacokinetics, and the fever response to interferon will be made. It is anticipated that patients with neutralizing antibodies will have some inhibition of all of these biological effects of interferon alfa-2a. Because all neutralizing antibodies detected in our patients neutralized only interferon alfa-2a and not a partially purified preparation of natural interferon, these patients will subsequently receive a dose of human lymphoblastoid interferon and these same biological end points determined. If, as is anticipated, patients do have normal biological responsiveness to human lymphoblastoid interferon in the face of antibodies to interferon alfa-2a, it will be concluded that hairy cell leukemia patients with disease resistance to recombinant interferon alfa-2a will likely be responsive to therapy with human lymphoblastoid interferon.